Project Summary The Pediatric Oncology Program has been continuously approved in the NCI Cancer Center Support Grant since 1992. The mission of the Program is to discover and develop targeted, rational treatment approaches to improve cure rates and reduce acute and long-term toxicities in children with cancer. The Programmatic goals are: 1) to define the genetic and cellular alterations involved in the pathogenesis of childhood cancers and to translate these discoveries into new diagnostics, biomarkers and therapeutic targets; 2) to develop and clinically test new immunotherapies that target tumor-specific antigens on childhood cancers; 3) to improve outcomes for childhood cancers by designing and conducting clinical trials of biologically targeted therapies, and by developing more rational methods of administering conventional therapies using pharmacokinetics and pharmacoepidemiology; and 4) to develop approaches to minimize the acute and long-term adverse effects of cancer treatment in children and adolescents using an integrated research approach incorporating psychosocial, survivorship and cancer control outcome measures. This Program was rated as ?Outstanding to Exceptional? at the time of the 2010 CCSG renewal application and is led by Frank Balis, MD, Professor of Pediatrics and Director of Clinical Cancer Research and Garrett Brodeur, MD, Professor of Pediatrics and Associate Director for Pediatric Research at the Abramson Cancer Center. Drs. Balis and Brodeur are experienced researchers and national leaders in childhood cancer research. The Pediatric Oncology Program has fully integrated basic, translational, and clinical research components, with a diverse group of investigators who have expertise and research efforts in cancer genomics, cell biology and signal transduction, tumor immunology and immunotherapy, drug development, clinical pharmacology, epidemiology, clinical research, cancer control, survivorship, and behavioral oncology. The Program is fully integrated into the Cancer Center. Pediatric oncologists are members of four other Programs, and Program members collaborate with investigators from five of the other Programs. The Pediatric Oncology Program is an international leader in clinical research and serves as the lead institution for the COG NCI Chair's grant. The 35 Program members represent five departments in the Perelman School of Medicine and have $16M in annual research grant funding, of which $6.4M is peer-reviewed and $2M is NCI-funded. There have been a total of 443 cancer- related publications from the Program since 2010. Of these, 35% are intra-Programmatic, 14% resulted from inter-Programmatic collaboration, and 71% are multi-institutional.